The nuclear envelope as a site of glucuronyltransferase in rat liver: properties of and effect of inducers on enzyme activity.
The formation of p-nitrophenylglucuronide from p-nitrophenol and [14C]uridine disphosphoglucuronic acid was demonstrated in intact rat liver nuclei and nuclear membranes. Most of the enzymatic activity in nuclei (80%) was localized in the nuclear envelope. Several in vitro activators of microsomal glucuronyltransferase had no effect on enzyme activity in whole nuclei, but were effective in stimulating the activity in nuclear membranes; however, the magnitude of activation (45%) was much less than with microsomes (500%). UDP-N-acetylglucosamine had no effect on nuclear UDP-glucuronyltransferase activity in whole nuclei or in nuclear membrane preparations. The nuclear membrane enzyme(s) did not obey simple Michaelis-Menten kinetics in native or detergent-activated enzyme preparations. The kinetic behavior did not change upon activation and the apparent Km values remained constant, 1.0 and 0.7 mM for UDP-glucuronic acid and nitrophenol, respectively. Nuclear membrane UDP-glucuronyltransferase activity was increased 3-fold by pretreatment with 3-methylcholanthrene. Phenobarbital or trans-stilbene oxide pretreatment had no effect on nuclear enzyme activity. In contrast, microsomal UDP-glucuronyltransferase activity was increased upon pretreatment with all of these inducers. The results suggest that rat hepatic nuclear glycuronyltransferase activity is localized in the nuclear envelope and that the activity is possibly under a different control mechanism than tha for the microsomes. The properties and physiological significance of the nuclear enzyme are discussed.
D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D009578:Nitrobenzenes / Q000378:metabolism; D009685:Nuclear Envelope / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains
D005965:Glucuronates; D009578:Nitrobenzenes; C002730:4-nitrophenylglucuronide; D014453:Glucuronosyltransferase